A gold catalyst for carbene-transfer reactions from ethyl diazoacetate

Article abstract of DOI:10.1002/anie.200501056

(Chemical Equation Presented) Approaching El Dorado: A gold catalyst has been discovered that transfers a carbene unit from ethyl diazoacetate to aromatic substrates (see scheme) as well as olefins, amines, and alcohols. The insertion of carbene units into the C-H bonds of the aromatic ring of benzene, toluene, and styrene is a novel reaction. R = H, CH₃, CH=CH ₂; IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene.

Full text of DOI:10.1002/anie.200501056

Communications
Carbene Chemistry
DOI: 10.1002/anie.200501056
A Gold Catalyst for Carbene-Transfer Reactions
from Ethyl Diazoacetate**
Manuel R. Fructos, Tomµs R. Belderrain,
Pierre de FrØmont, Natalie M. Scott, Steven P. Nolan,*
M. Mar Díaz-Requejo,* and Pedro J. PØrez*
The use of transition-metal-based catalysts for the transfer of
carbene units from diazo compounds constitutes a powerful
[
1]
tool in organic synthesis. Several metals have been reported
to mediate this transformation effectively, and the appropri-
ate selection of ligands has permitted excellent selectivities.
Highly chemo-, diastereo-, and/or enantioselective systems
have been reported with rhodium-, copper-, or cobalt-
containing catalysts. In fact, nearly all 12 elements of
Groups 8–11 have been found to decompose diazo com-
pounds and transfer a carbene unit to saturated or unsatu-
[
2]
rated organic substrates, leading to the insertion or addition
product, respectively (Scheme 1). Only one of these 12
[
3]
elements remains unexplored in this chemistry: gold.
Although the other members of Group 11—copper and, to
a lesser extent, silver—have been described to induce such
transformations, conducting this type of catalytic reaction
with gold remains a challenge. We therefore focused our
attention on the development of a gold-based catalyst, as a
result of our experience in the area of metal-catalyzed
[
4]
carbene transfer from ethyl diazoacetate (EDA).
We recently reported the catalytic behavior of [(IPr)CuCl]
(1, IPr= 1,3-bis(diisopropylphenyl)imidazol-2-ylidene) for
the transfer of carbene from ethyl diazoacetate to olefins,
amines, and alcohols to form cyclopropanes, amino acid
[
5]
derivatives, and ethers, respectively. These promising results
[*] P. de FrØmont, N. M. Scott, Prof. Dr. S. P. Nolan
Department ofChemistry
University ofNew Orleans
New Orleans, LA 70148 (USA)
Fax: (+1)504-280-6860
E-mail: snolan@uno.edu
M. R. Fructos, Dr. T. R. Belderrain, Dr. M. M. Díaz-Requejo,
Prof. Dr. P. J. PØrez
Departamento de Química y Ciencia de los Materiales
Campus de El Carmen s/n
Universidad de Huelva–Unidad Asociada al CSIC
21007 Huelva (Spain)
Fax: (+34)959-219-942
E-mail: mmdiaz@dqcm.uhu.es
perez@dqcm.uhu.es
[**] We are grateful for financial support for this work (BQU2002–
01114). We acknowledge the Universidad de Huelva (NMR Service),
the MECD (M.R.F.), and the Ramon y Cajal Program (M.M.D.R.) as
well as the National Science Foundation for work conducted at the
University ofNew Orleans.
Supporting information for this article (general experimental
procedures and product characterization data) is available on the
WWW under http://www.angewandte.org or from the author.
5
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Chemie
Once prepared and characterized, complex
2 was
employed as a catalyst for the cyclopropanation of styrene
with ethyl diazoacetate, a well-known model reaction. Our
previous work with the copper complex 1 suggested that the
chloride ion had to be removed from the metal center prior to
[
5]
reaction with EDA. We therefore employed a modified
method in which the active catalytic species was generated
in situ by using an equimolar mixture of 2 and the sodium salt
of the non-coordinating anion tetrakis(3,5-bis(trifluorome-
thyl)phenyl)borate (BAr’ ). The use of a 2.5% catalyst
4
loading (with respect to EDA) in neat styrene (1 mL) led to
the consumption of EDA within a few minutes (see the
Experimental Section). Analysis of the reaction mixture by
GC and GCMS showed, besides the expected cis- and trans-
cyclopropanes, three other products with the same molar
mass, namely, the o, m, and p isomers of the styryl acetate
shown in Equation (2). These additional products are formed
Scheme 1. Top left: Catalytic cycle proposed for the metal-catalyzed
decomposition ofdiazo compounds and subsequent carbene trans ef r
to a saturated or unsaturated substrate (SD). Top right: Metals of
Groups 8–11 that have been described to induce such a transforma-
tion; gold still remained unreported. Bottom: The most common
examples oforganic trans of rmations using the methodology ofcar-
bene transfer from diazo compounds.
prompted us to examine the potential role of the gold
analogue [(IPr)AuCl] (2), which was prepared from equimo-
[
6]
lar amounts of the IPr ligand and [AuCl(SMe )] [Eq. (1)].
2
This new compound was spectroscopically characterized, and
its structure confirmed by X-ray diffraction studies (Figure 1).
The gold(i) atom is two-coordinate in an essentially linear
environment with C-Au-Cl bond angles close to 1808, an
arrangement similar to that previously found for 1.
2
by the formal insertion of the DCHCO Et unit into the sp Cꢀ
2
Hbond of the aromatic ring of the styrene. To the best of our
knowledge, this type of intermolecular reaction is unprece-
[
7]
dented. All published reports have shown that the double
bond of styrene is preferentially converted into the cyclo-
propane product in this reaction. A second, but nonetheless
important feature of this gold catalyst is that no diethyl
fumarate or maleate formed as a result of EDA coupling,
even though the diazo compound was added to the reaction
mixture in one portion.
To see whether this unexpected insertion reaction can be
generalized, we examined two common aromatic substrates,
benzene and toluene [Eqs. (3), (4); yields determined by
NMR spectroscopy]. Previous reports have shown that the
metal-catalyzed addition of EDA to these compounds results
in the formation of cycloheptatriene rings as the major
[
4h,8]
product.
In the case of toluene, a few catalysts have also
promoted insertion into the methyl CꢀHbond to provide the
[
4h,8,9]
2
dihydrocinnamate derivative
but there are no examples
of insertion into the aromatic sp CꢀHbond. In contrast, the
Figure 1. Ball-and-stick view ofcomplex 2; hydrogen atoms have been
omitted for clarity.
0
use of 2 and NaBAr as the catalyst precursor for the reaction
4
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Communications
of EDA and benzene led to a mixture of the expected
cycloheptatriene as well as ethyl phenylacetate [Eq. (3)], the
latter formed by formal insertion into the aromatic CꢀH
bond. Similar behavior was observed with toluene as the
substrate [Eq. (4)]: The expansion products were observed
along with the three isomers of ethyl tolylacetate. The
identities of the new products are unambiguous, as their
spectroscopic and chromatographic data are identical to those
of commercial samples (see the Experimental Section).
No EDA-coupling products—that is, diethyl fumarate and
maleate—were observed in the above transformations, high-
lighting the chemoselectivity of this catalytic system. Even
allowing EDA to react with complex 2 at room temperature
for several hours did not lead to any transformation of the
initial diazo compound. Heating of the reaction mixture at
6
08C and 808C did not induce any Au-catalyzed EDA
decomposition, therefore indicating the stability of the
diazo compound in the presence of 2, as was observed for
[
5]
the copper analogue 1.
We next screened several substrates to explore the range
of activity for the gold system (Table 1). The use of cis-
0
Table 1: The addition or insertion ofEDA catalyzed by 2 + NaBAr .
4
[
a]
Substrate
Product
Yield [%]
[
b]
>
>
99
99
[
b]
[
b]
>
99
Figure 2. Top: Plot showing the consumption ofEDA in the reaction of
methanol and ethyl diazoacetate with 2 as catalyst in the absence (
&
)
[
[
c]
c]
0
CH OH
CH OCH CO Et
>99
>99
and presence ofNaBAr (!). Inset: Plot ofln[EDA] versus time t from
3
3
2
2
4
CH CH OH
CH CH OCH CO Et
which the following k values were obtained: 2 as catalyst:
3
2
3
2
2
2
obs
ꢀ4
ꢀ1
0
ꢀ4 ꢀ1
kobs =5.98”10
s
; 2 + NaBAr as catalyst: k =6.84”10
s .
4
obs
[
a] No diethyl fumarate or maleate was detected in any experiment; see
Bottom: Plot ofnitrogen evolution under the same conditions.
the Experimental Section for details. [b] Determined by NMR spectros-
copy at the end ofthe reaction using an internal standard. [c] Determined
by GC using an internal standard.
ꢀ4
Exponential fitting provided the following values: k =7.94”10
obs
ꢀ3
ꢀ1
0
(2 as catalyst, A), kobs =1.05”10
s
(2 + NaBAr as catalyst, B).
4
ꢀ
3
ꢀ1
1
.05 ” 10 s , respectively). These values compare well with
cycloctene as the olefin provided the expected mixture of exo-
and endo-cyclopropanes. The insertion of EDA into NꢀHand
OꢀHbonds was also studied with amines and alcohols; in all
those obtained from monitoring EDA consumption.
Scheme 2 illustrates a possible explanation for the exper-
imental kinetic data. A cationic species C, probably contain-
cases the corresponding amino acid derivatives and ethers
were obtained quantitatively. Again, no EDA coupling
products were detected in the mixture at the end of the
reaction.
ing coordinated methanol, is formed in both instances. The
0
addition of NaBAr promotes the quantitative conversion of 2
4
0
into such a species; however, in the absence of NaBAr , an
4
equilibrium between the neutral 2 and the cationic C takes
place. This also explains the slightly more sluggish reaction
with 2 as catalyst since the amount of C is not equal to the
Kinetic experiments were performed using methanol as
the substrate with complex 2 as the catalyst precursor both
0
with and without the halide scavenger NaBAr . First, the
4
consumption of EDA was monitored in parallel experiments
0
differing only in the presence or absence of NaBAr . The two
4
reactions lead to very similar decays that correspond to first-
order behavior (Figure 2). Plots of ln[EDA] versus time
ꢀ
4
ꢀ4 ꢀ1
provided kobs values of 5.98 ” 10 and 6.84 ” 10
s
for the
experiments carried out in the absence and in the presence of
the tetraarylborate anion, respectively; the latter reaction is
slightly faster but of the same order of magnitude. Nearly
identical values for kobs were obtained from experiments in
Scheme 2. Proposed mechanism for the generation of the catalytic
species.
ꢀ
4
which the nitrogen evolution was measured (7.94 ” 10 and
5
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Angewandte
Chemie
initial amount of 2. In contrast, the use of the arylborate salt
ensures that [C] = [2]init. The catalytic cycle starts from C, and
the rate-determining step is the formation of a metallocar-
bene intermediate, as commonly proposed for this type of
transformation. . The observation of very similar rate
constants from the monitoring of nitrogen generation and
EDA consumption is in line with the absence of fumarate and
maleate products.
the products (see the Supporting Information). To establish the mass
balance, an internal standard was employed.
Received: March 23, 2005
Revised: May 12, 2005
Published online: July 22, 2005
[
1]
Keywords: CꢀH activation · carbenes · diazo compounds · gold ·
.
homogeneous catalysis
In conclusion, we have described the first example of a
gold-based catalyst for the decomposition of ethyl diazoace-
tate and the subsequent transfer of the DCHCO Et unit to
2
[1] M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds, Wiley, New York,
1998.
saturated and unsaturated substrates: Cyclopropanation of
olefins as well as insertion into NꢀHand O ꢀHbonds have
[
2] a) See reference [1] for examples based on Fe, Ru, Os, Co, Rh,
Ni, Pd, Pt, and Cu; b) for iridium as catalyst, see: T. Kubo, S.
Sakagushi, Y. Ishii, Chem. Commun. 2000, 625; c) for Ag-based
catalysts, see: J. Urbano, T. R. Belderraín, M. C. Nicasio, S.
Trofimenko, M. M. Díaz-Requejo, P. J. PØrez, Organometallics
been achieved. Even more interesting is the novel insertion of
the carbene units into the CꢀHbonds of the aromatic ring of
benzene, toluene, and styrene. Finally, this catalyst is very
chemoselective, since no EDA coupling products are
observed in any of the reactions studied.
2005, 24, 1528, and references therein.
[
3] For gold-based catalysts for other processes, see: a) A. S. K.
Hashmi, Gold Bull. 2004, 37, 51; b) A. S. K. Hashmi, J. P.
Weyrauch, M. Rudolph, E. Kurpejovi c´ , Angew. Chem. 2004,
116, 6707; Angew. Chem. Int. Ed. 2004, 43, 6545; c) Z. Shi, C. He,
J. Org. Chem. 2004, 69, 3669; d) J. J. Kennedy-Smith, S. T.
Staben, F. D. Toste, J. Am. Chem. Soc. 2004, 126, 4526; e) C.
Nieto-Oberhuber, M. P. Muꢀoz, E. Buꢀuel, C. Nevado, D. J.
Cꢁrdenas, A. M. Echavarren, Angew. Chem. 2004, 116, 2456;
Angew. Chem. Int. Ed. 2004, 43, 2402; f) V. Mamane, T. Gress,
H.; Krause, A. Furstner, J. Am. Chem. Soc. 2004, 126, 8654; g) N.
Morita, N. Krause, Org. Lett. 2004, 6, 4121; h) R. Casado, M.
Contel, M. Laguna, P. Romero, S. Sanz, J. Am. Chem. Soc. 2003,
125, 11925; i) G. B. Shulꢂpin, A. E. Shilov, G. Sꢃss-Fink, Tetra-
hedron Lett. 2001, 42, 7253; j) G. Dyker, Angew. Chem. 2000,
112, 4407; Angew. Chem. Int. Ed. 2000, 39, 4237; k) D.
Thompson, Gold Bull. 1999, 32, 12; l) J. H. Teles, S. Brode, M.
Chabanas, Angew. Chem. 1998, 110, 1475; Angew. Chem. Int. Ed.
1998, 37, 1415.
Experimental Section
General: All reactions were carried out by using standard Schlenk
techniques under an atmosphere of dry argon or in an MBraun
glovebox containing dry argon or nitrogen. Anhydrous solvents were
purchased from Aldrich and degassed prior to use. CD Cl was either
2
2
dried over CaH , or degassed with argon and dried over molecular
2
sieves. The reagents (olefins, alcohols, amines) were also purchased
from Aldrich and employed without further purification. IPr was
synthesized by deprotonation of the imidazolium salt with base
according to a literature procedure.
IPr·HCl, can be purchased from Strem Chemicals Inc. The Hand
[
10]
The immediate precursor,
1
13
C
NMR spectra were collected on 400-MHz Varian Gemini and Varian
Mercury spectrometers. The GC and GCMS were obtained in Varian
3
800 and Saturn 2100 instruments, respectively. Elemental analyses
were performed by Robertson Microlit Laboratories, Madison, NJ.
: In a glove box a 100-mL Schenk flask was charged with IPr
[4] For olefin cyclopropanation, see: a) M. M. Díaz-Requejo, T. R.
Belderrain, S. Trofimenko, P. J. PØrez, J. Am. Chem. Soc. 2001,
123, 3167; b) M. M. Díaz-Requejo, A. Caballero, T. R. Belder-
rain, M. C. Nicasio, S. Trofimenko, P. J. PØrez, J. Am. Chem. Soc.
2002, 124, 978; For alkyne cyclopropenation, see: c) M. M. Díaz-
Requejo, M. A. Mairena, T. R. Belderrain, M. C. Nicasio, S.
Trofimenko, P. J. PØrez, Chem. Commun. 2001, 1804; for CꢀH
2
(
(
686 mg, 1.8 mmol) and THF (35 mL), and then [AuCl(SMe )]
232 mg, 0.80 mmol) was added. The resulting solution was stirred
2
at room temperature for 12 h. The solvent was removed under
vacuum, and CH Cl (5 mL) was added. The colorless solution was
filtered, and hexane (10 mL) was added to the filtrate, resulting in
2
2
insertion, see: d) M. M. Díaz-Requejo, T. R. Belderrain, M. C.
Nicasio, S. Trofimenko, P. J. PØrez, J. Am. Chem. Soc. 2002, 124,
896; e) A. Caballero, M. M. Díaz-Requejo, T. R. Belderrain,
M. C. Nicasio, S. Trofimenko, P. J. PØrez, J. Am. Chem. Soc. 2003,
125, 1446; N-Hinsertion: f) M. E. Morilla, M. M. Díaz-Requejo,
T. R. Belderrain, M. C. Nicasio, S. Trofimenko, P. J. PØrez, Chem.
Commun. 2002, 2998; g) for OꢀHinsertion, see: M. E. Morilla,
precipitation of an off-white solid. The solid was washed with hexane
1
(
(
7
3 ” 5 mL) and dried under vacuum. Yield: 770 mg (69%). HNMR
400 MHz, CD Cl ): d = 7.57 (t, J = 7.8 Hz, 2H; ArH), 7.35 (d, J =
.8 Hz, 4H; ArH), 7.24 (s, 2H; Imid-H), 2.57 (septet, J = 6.8 Hz, 4H;
2
2
CH(CH ) ), 1.34 (d, J = 6.8 Hz, 12H; CH(CH ) ), 1.23 ppm (d, J =
3
2
3 2
1
3
1
6
.8 Hz, 12H; CH(CH ) ); C{ H} NMR (125 MHz, CD Cl ): d =
3
2
2
2
1
75.09 (Ccarbene), 145.78 (CAr), 134.05 (C ), 130.68 (CAr), 124.28
M. J. Molina, M. M. Díaz-Requejo, T. R. Belderrain, M. C.
Nicasio, S. Trofimenko, P. J. PØrez, Organometallics 2004, 23,
2914; for addition to aromatic rings, see: h) M. E. Morilla, M. M.
Díaz-Requejo, T. R. Belderrain, M. C. Nicasio, S. Trofimenko,
P. J. PØrez, Organometallics 2004, 23, 293.
Ar
(
(
5
CAr), 123.32 (Cimid), 28.79 (CH(CH ) ), 24.17 (CH(CH ) ), 23.74 ppm
CH(CH ) ); elemental analysis: calcd for C H N AuCl (621.69): C
2.11, H5.79, N 4.50; found: C 51.70, H5.61, N 4.38. Suitable crystals
3
2
3 2
3
2
27 36
2
for crystallographic study were grown by slow evaporation of a
saturated solution in acetone. CCDC-258274 (2) contains the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from the Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[5] M. R. Fructos, T. R. Belderrain, M. C. Nicasio, S. P. Nolan, H.
Kaur, M. M. Díaz-Requejo, P. J. PØrez, J. Am. Chem. Soc. 2004,
126, 10846.
[6] See the Supporting Information for synthetic and structural
details. For other members of the [(NHC)AuCl] family, see: P.
de FrØmont, N. M. Scott, E. D. Stevens, S. P. Nolan, Organo-
metallics 2005, 24, in press.
Catalytic experiments: The precatalyst 2 (0.025 mmol) was
[
11]
dissolved in neat substrate (1–3 mL), and NaBAr’4 (1 equiv) was
added to the solution. After 15 min of stirring, EDA (0.5 mmol) was
added in one portion. After 1 h of additional stirring, the mixture was
analyzed by GC and GCMS. The volatile components were then
removed, and the residue analyzed by NMR spectroscopy to identify
[7] The intramolecular insertion of diazo ketones into aromatic Cꢀ
Hbonds has been extensively reported (see reference [1]). This
process has been described as an electrophilic addition of the
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metallocarbene followed by 1,2-hydride migration: A. Padwa,
D. J. Austin, A. T. Price, M. A. Semones, M. P. Doyle, M. N.
Protopopova, W. R. Winchester, A. Tarn, J. Am. Chem. Soc.
1993, 115, 8669. The observed ratios for the products, partic-
ularly the meta/para ratios (lower than 2:1), shows a preference
for the para position, a fact that would be in accord with such
proposal.
[
8] A. J. Anciaux, A. Demonceau, A. F. Noels, A. J. Hubert, R.
Warin, P. H. Teyssie, J. Org. Chem. 1981, 46, 873.
9] H. J. Callot, F. Metz, Nouv. J. Chim. 1985, 9, 167.
[
[
[
10] M. S. Viciu, O. Navarro, R. F. Germaneau, R. A. Kelly III, W.
Sommer, N. Marion, E. D. Stevens, L. Cavallo, S. P. Nolan,
Organometallics 2004, 23, 1629, and references therein.
11] M. Brookhart, B. Grant, A. F. Volpe, Organometallics 1992, 11,
3920.
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Angew. Chem. Int. Ed. 2005, 44, 5284 –5288